Breathing Frequency Research Articles

Diagnosis of Empyema as a Complication of Liver Abscess in Peripheral Area

Right pleural empyema is one of the rare complications in liver abscess. This condition is life-threatening as it causes breathing difficulties and requires immediate life-saving. This case report aims to diagnose and manage empyema in a male patient with a liver abscess in a limited diagnostic setting. Methods: According to medical records, a 44-year-old man came to the emergency room (ER) of Umbu Rara Meha General Hospital with complaints of shortness of breath that had been getting worse for two months, accompanied by a cough with phlegm for one week, fever, and weight loss. The patient also complained of pain in the right upper abdomen for the last four months. History of pulmonary tuberculosis, diabetes mellitus, or hypertension was denied. The patient is not a smoker. On physical examination, there was an increase in the frequency of breathing and a decrease in the vesicular sounds on the right side. Right thorax X-ray examination revealed massive right pleural effusion without pulmonary infiltrates. Abdominal ultrasound showed a liver abscess. Emergency pleural puncture was performed in the ER, and 1600 cc of purulent pleural fluid was removed, followed by Water Sealed Draignase (WSD) installation. The patient was given intravenous broad-spectrum antibiotics and treated for 12 days. Conclusion: Empyema can be a rare but life-threatening complication of liver abscess. Medical action must be taken immediately in the ER to save the patient. Delaying pus drainage can increase morbidity and mortality rates.

Analysis of the effect of inert gas on alveolar/venous blood partial pressure by using the operator splitting method.

This study aims to investigate how inert gas affects the partial pressure of alveolar and venous blood using a fast and accurate operator splitting method (OSM). Unlike previous complex methods, such as the finite element method (FEM), OSM effectively separates governing equations into smaller sub-problems, facilitating a better understanding of inert gas transport and exchange between blood capillaries and surrounding tissue. The governing equations were discretized with a fully implicit finite difference method (FDM), which enables the use of larger time steps. The model employed partial differential equations, considering convection-diffusion in blood and only diffusion in tissue. The study explores the impact of initial arterial pressure, breathing frequency, blood flow velocity, solubility, and diffusivity on the partial pressure of inert gas in blood and tissue. Additionally, the effects of anesthetic inert gas and oxygen on venous blood partial pressure were analyzed. Simulation results demonstrate that the high solubility and diffusivity of anesthetic inert gas lead to its prolonged presence in blood and tissue, resulting in lower partial pressure in venous blood. These findings enhance our understanding of inert gas interaction with alveolar/venous blood, with potential implications for medical diagnostics and therapies.

A switched-gain nonlinear observer for estimation of thoracoabdominal displacements and detection of asynchrony

This paper develops and evaluates a wearable sensor-based system for the estimation of three-dimensional thoracoabdominal displacements and the detection of respiratory asynchrony between chest and abdomen. Such estimation is useful for a number of respiratory diagnosis applications, including detection of paradoxical breathing, quantification of tidal volume, and decision-support for initiation of, or weaning from, mechanical ventilation. The use of inertial sensors on the body to estimate respiratory displacements is challenging due to the tilting of the body that occurs with breathing, causing continuous changes in the gravity component at the same frequency as the breathing frequency. A method to estimate the front-to-back and side-to-side tilt angles is developed using a nonlinear observer. Due to the complex multivariable nonlinear measurement functions involved, a switched gain nonlinear observer is found to be necessary. The global stability of the observer is analyzed using Lyapunov analysis. Respiratory asynchrony is evaluated using Lissajous curves and a cross correlation phase angle calculation method. Example experimental results are presented using data from three subjects at various breathing frequencies, tidal volumes, and inspiratory resistances. Displacement estimates are found to be typically within ± 1 mm compared to a gold standard reference for most data sets. Phase angles are found to increase monotonically with inspiratory resistive or elastic loading.

The Utility of Heartrate and Heartrate Variability Biofeedback for the Improvement of Interoception across Behavioural, Physiological and Neural Outcome Measures: A Systematic Review.

Interoceptive dysfunctions are increasingly implicated in a number of physical and mental health conditions. Accordingly, there is a pertinent need for therapeutic interventions which target interoceptive deficits. Heartrate and heartrate variability biofeedback therapy (HR(V)-BF), interventions which train individuals to regulate their cardiovascular signals and constrain these within optimal parameters through breathing, could enhance the functioning of interoceptive pathways via stimulation of the vagus nerve. Consequently, this narrative systematic review sought to synthesise the current state of the literature with regard to the potential of HR(V)-BF as an interoceptive intervention across behavioural, physiological and neural outcome measures related to interoception. In total, 77 papers were included in this review, with the majority using physiological outcome measures. Overall, findings were mixed with respect to improvements in the outcome measures after HR(V)-BF. However, trends suggested that effects on measures related to interoception were stronger when resonance frequency breathing and an intense treatment protocol were employed. Based on these findings, we propose a three-stage model by which HR(V)-BF may improve interoception which draws upon principles of interoceptive inference and predictive coding. Furthermore, we provide specific directions for future research, which will serve to advance the current knowledge state.

Could breathing frequency become a pragmatic means to monitor exercise intensity in atrial fibrillation and coronary heart disease?

Could breathing frequency become a pragmatic means to monitor exercise intensity in atrial fibrillation and coronary heart disease?

Emergency Response Person Localization and Vital Sign Estimation Using a Semi-Autonomous Robot Mounted SFCW Radar.

The large number and scale of natural and man-made disasters have led to an urgent demand for technologies that enhance the safety and efficiency of search and rescue teams. Semi-autonomous rescue robots are beneficial, especially when searching inaccessible terrains, or dangerous environments, such as collapsed infrastructures. For search and rescue missions in degraded visual conditions or non-line of sight scenarios, radar-based approaches may contribute to acquire valuable, and otherwise unavailable information. This article presents a complete signal processing chain for radar-based multi-person detection, 2D-MUSIC localization and breathing frequency estimation. The proposed method shows promising results on a challenging emergency response dataset that we collected using a semi-autonomous robot equipped with a commercially available through-wall radar system. The dataset is composed of 62 scenarios of various difficulty levels with up to five persons captured in different postures, angles and ranges including wooden and stone obstacles that block the radar line of sight. Ground truth data for reference locations, respiration, electrocardiogram, and acceleration signals are included.

Physiological Effects of High-Flow Tracheal Oxygen in Tracheostomized Patients Weaning From Mechanical Ventilation.

High-flow tracheal oxygen (HFTO) is being used as supportive therapy during weaning in tracheostomized patients difficult to wean from invasive mechanical ventilation. There is, however, no clinical evidence for such a strategy. Therefore, we conducted a systematic review to summarize studies evaluating the physiologic effects of HFTO during tracheostomy-facilitated weaning and to identify potential areas for future research in this field. Observational and interventional studies on critically ill subjects weaning from mechanical ventilation via tracheostomy published until December 22, 2022, were eligible. Studies on high-flow oxygen, only in children, non-human models or animals, on clinical outcome only, abstracts without full-text availability, case reports, and reviews were excluded. Main outcomes were end-expiratory lung volume (EELV) and tidal volume using electrical impedance tomography, respiratory effort assessed by esophageal manometry, work of breathing and neuroventilatory drive as assessed by electrical activity of the diaphragm (EAdi) signal, airway pressure (Paw), oxygenation (PaO2 /FIO2 or SpO2 /FIO2 ), breathing frequency, tidal volume, and PaCO2 . In total, 1,327 references were identified, of which 5 were included. In all studies, HFTO was administered with flow 50 L/min and compared to conventional O2 therapy in a crossover design. The total average duration of invasive ventilation at time of measurements ranged from 11-27 d. In two studies, PaO2 /FIO2 and mean Paw were higher with HFTO. EELV, tidal volumes, esophageal pressure swings, and EAdi were similar during high-flow tracheal oxygen and conventional O2 therapy. The main physiological effect of HFTO as compared to conventional O2 therapy in tracheostomized subjects weaning from mechanical ventilation was improved oxygenation that is probably flow-dependent. Respiratory effort, lung aeration, neuroventilatory drive, and ventilation were similar for HFTO and conventional O2 therapy. Future studies on HFTO should be performed early in the weaning process and should evaluate its effect on sputum clearance and patient-centered outcomes like dyspnea.

Rosmarinic acid alleviates septic acute respiratory distress syndrome in mice by suppressing the bronchial epithelial RAS-mediated ferroptosis

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein–protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.

Self-Powered cobalt nanocluster decorated flexible graphene based Tribo-Sensors for respiratory diagnosis of critical asthma patient

Self-powered ultrafast sensors have received much attention for sustainable operation without any external power source in the Internet of Things (IoT) platform. This paper proposes faster responsive, highly sensitive triboelectric nanogenerator (TENG) sensors based on few layered nitrogen-doped graphene anchored with cobalt nanocluster (Co-N-Gr) to detect the relative concentration of target species, their proximity analysis, and monitor malfunction of human respiration in real-time. Herein, to understand the sensing mechanism, P-type behaviour of this active material is verified under the FET platform by reducing the leakage current density via the implementation of dual dielectric gate (NiO (200 nm)-SiO2 (10 nm)) oxides leading to better control over channel mobility. The device exhibits maximum sensitivity of around 4722 % at zero bias conditions with excellent response and recovery time of 1.16 s and 1.39 s, respectively which falls within the range of standard human breathing frequency. The triboelectric nature of the sensor device at 1 V bias under natural breathing exhibits a high sensitivity (39.56 %) towards relative humidity of 10–90 % with excellent stability over 13 h. In addition, our TENG sensor is highly sensitive towards NOx content upto ppb levelwhich can improve reliability towards asthma detection as NOx content is relatively higher in asthma patients. This approach provides an integrated platform not only towards selective detection of NOx content as well as to identify the individual breathing strength. Furthermore, as-fabricated self-powered device demonstrates its potential in differentiating various respiratory status and has the capability to detect acute exacerbation of chronic obstructive pulmonary disease (AECOPD) via a distinct pattern recognition. Therefore, the work paves the way to design a low-cost flexible device fabrication on Kapton substrate integrable with wearable appliances for commercialization.

Eccentric Exercise-Induced Muscle Damage Reduces Gross Efficiency.

The effect of eccentric exercise-induced muscle damage (EIMD) on cycling efficiency is unknown. The aim of the present study was to assess the effect of EIMD on gross and delta efficiency and the cardiopulmonary responses to cycle ergometry. Twenty-one recreational athletes performed cycling at 70%, 90%, and 110% of the gas exchange threshold (GET) under control conditions (Control) and 24 h following an eccentric damaging protocol (Damage). Knee extensor isometric maximal voluntary contraction, potentiated twitch ( Qtw,pot ), and voluntary activation were assessed before Control and Damage. Gross and delta efficiency were assessed using indirect calorimetry, and cardiopulmonary responses were measured at each power output. Electromyography root-mean-square (EMG RMS ) during cycling was also determined. Maximal voluntary contraction was 25% ± 18% lower for Damage than Control ( P < 0.001). Gross efficiency was lower for Damage than Control ( P < 0.001) by 0.55% ± 0.79%, 0.59% ± 0.73%, and 0.60% ± 0.87% for 70%, 90%, and 110% GET, respectively. Delta efficiency was unchanged between conditions ( P = 0.513). Concurrently, cycling EMG RMS was higher for Damage than Control ( P = 0.004). An intensity-dependent increase in breath frequency and V̇ E /V̇CO 2 was found, which were higher for Damage only at 110% GET ( P ≤ 0.019). Thus, gross efficiency is reduced following EIMD. The concurrently higher EMG RMS suggests that increases in muscle activation in the presence of EIMD might have contributed to reduced gross efficiency. The lack of change in delta efficiency might relate to its poor reliability hindering the ability to detect change. The findings also show that EIMD-associated hyperventilation is dependent on exercise intensity, which might relate to increases in central command with EIMD.

Lung Volume and Ventilation Distribution After Bariatric Surgery: High-Flow Nasal Cannula Versus CPAP.

Patients with obesity are at increased risk of postoperative pulmonary complications. CPAP has been used successfully to prevent and treat acute respiratory failure, but in many clinical scenarios, high-flow nasal cannula (HFNC) therapy is emerging as a possible alternative. We aimed to compare HFNC and CPAP in a sequential study measuring their effects on gas exchange, lung volumes, and gas distribution within the lungs measured through electrical impedance tomography (EIT). We enrolled 15 subjects undergoing laparoscopic bariatric surgery. Postoperatively they underwent the following oxygen therapy protocol (10 min/step): baseline air-entrainment mask, HFNC at increasing (40, 60, 80, and 100 L/min) and decreasing flows (80, 60, and 40 L/min), washout air-entrainment mask and CPAP (10 cm H2O). Primary outcome was the change in end-expiratory lung impedance (ΔEELI) measured by EIT data processing. Secondary outcomes were changes of global inhomogeneity (GI) index and tidal impedance variation (TIV) measured by EIT, arterial oxygenation, carbon dioxide content, pH, respiratory frequency, and subject's comfort. Thirteen subjects completed the study. Compared to baseline, ΔEELI was higher during 10 cm H2O CPAP (P = .001) and HFNC 100 L/min (P = .02), as well as during decreasing flows HFNC 80, 60, and 40 L/min (P = .008, .004, and .02, respectively). GI index was lower during HFNC 100 compared to HFNC 60increasing (P = .044), HFNC 60decreasing (P = .02) HFNC 40decreasing (P = .01), and during 10 cm H2O CPAP compared to washout period (P = .01) and HFNC 40decreasing (P = .03). TIV was higher during 10 cm H2O CPAP compared to baseline (P = .008). Compared to baseline, breathing frequency was lower at HFNC 60increasing, HFNC 100, and HFNC 80decreasing (P = .01, .02, and .03, respectively). No differences were detected regarding arterial oxygenation, carbon dioxide content, pH, and subject's comfort. HFNC at a flow of 100 L/min induced postoperative pulmonary recruitment in bariatric subjects, with no significant differences compared to 10 cm H2O CPAP in terms of lung recruitment and ventilation distribution.

Comparison of Forward-Leaning and Fowler Position: Effects on Vital Signs, Pain, and Anxiety Scores in Children With Asthma Exacerbations.

It is essential to relieve bronchospasm or specific asthma symptoms by administering immediate inhaler treatment during an asthma exacerbation. The present study compared the effect of Fowler position and forward-leaning positions during nebulization on heart rate, SpO2 , breathing frequency, pain, and anxiety levels in children experiencing asthma exacerbations. The data originated from a randomized trial that compared 86 participants (study group n = 43, control group n = 43) who presented to the pediatric emergency department with asthma exacerbations between October 2019-February 2020. The subjects were administered nebulization 3 times, during which the study group was placed in the forward-leaning position and the control group in the routine Fowler position. The subjects provided information on chest pain and anxiety levels before and after nebulization, and heart rate, SpO2 , and breathing frequency were measured before and after each nebulization. The difference in the mean SpO2 measured at admission and after the third nebulization was significantly higher (3.2 ± 1.5% vs 2.3 ± 1.9%, P = .01); the difference in the mean breathing frequency was considerably higher (-6.0 ± 1.7 breaths/min vs -3.2 ± 1.8 breaths/min, P < .001), and the difference in the mean pain scores was significantly higher (-3.3 ± 2.5 vs -2.0 ± 2.3, P = .02) in the study group than in the control group. In addition, after the third nebulization, the breathing frequency (22.8 ± 2.8 breaths/min vs 24.2 ± 2.7 breaths/min, P = .02) and pain score of the study group were lower (0.8 ± 1.3 vs 1.5 ± 1.5, P = .01). There was no difference in the mean heart rate (20.6 ± 16.2 beats/min vs 20.0 ± 15.4 beats/min, P = .85) and anxiety levels (-2.0 ± 2.2 vs -1.9 ± 2.2, P = .90) between the groups. Placing children in a forward-leaning position during nebulization was effective in improving SpO2 and reducing breathing frequency and chest pain. The forward-leaning position implemented during nebulization is a non-pharmacologic method that supports recovery in children with asthma exacerbations.

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia.

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated sympathetic activity to the cardiovascular system leading to hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. This study investigates the role of the postinspiratory complex (PiCo) and preBötzinger complex (preBötC) in respiratory-sympathetic coupling under control conditions and following exposure to chronic intermittent hypoxia (CIH) for 21 days (5% O2-80 bouts/day). The surface of the ventral brainstem was exposed in urethane (1.5 g/kg) anesthetized, spontaneously breathing adult mice. Cholinergic (ChAT), glutamatergic (Vglut2), and neurons that co-express ChAT and Vglut2 at PiCo, as well as Dbx1 and Vglut2 neurons at preBötC, were optogenetically stimulated while recording activity from the diaphragm (DIA), vagus nerve (cVN), and cervical sympathetic nerve (cSN). Following CIH exposure, baseline cSN activity increased, breathing frequency increased, and expiratory time decreased. In control mice, stimulating PiCo specific cholinergic-glutamatergic neurons caused a sympathetic burst during all phases of the respiratory cycle, whereas optogenetic activation of cholinergic-glutamatergic PiCo neurons in CIH mice increased sympathetic activity only during postinspiration and late expiration. Stimulation of glutamatergic PiCo neurons increased cSN activity during the postinspiratory phase in control and CIH mice. Optogenetic stimulation of ChAT containing neurons in the PiCo area did not affect sympathetic activity under control or CIH conditions. Stimulating Dbx1 or Vglut2 neurons in preBötC evoked an inspiration and a concomitant cSN burst under control and CIH conditions. Taken together, these results suggest that PiCo and preBötC contribute to respiratory-sympathetic coupling, which is altered by CIH, and may contribute to the hypertension observed in patients with OSA.

Is breathing frequency a potential means for monitoring exercise intensity in people with atrial fibrillation and coronary heart disease when heart rate is mitigated?

PurposeModerate-intensity aerobic exercise is safe and beneficial in atrial fibrillation (AF) and coronary heart disease (CHD). Irregular or rapid heart rates (HR) in AF and other heart conditions create a challenge to using HR to monitor exercise intensity. The purpose of this study was to assess the potential of breathing frequency (BF) to monitor exercise intensity in people with AF and CHD without AF.MethodsThis observational study included 30 AF participants (19 Male, 70.7 ± 8.7 yrs) and 67 non-AF CHD participants (38 Male, 56.9 ± 11.4 yrs). All performed an incremental maximal exercise test with pulmonary gas exchange.ResultsPeak aerobic power in AF (V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\dot{\ ext{V}}}$$\\end{document}O2peak; 17.8 ± 5.0 ml.kg−1.min−1) was lower than in CHD (26.7 ml.kg−1.min−1) (p < .001). BF responses in AF and CHD were similar (BF peak: AF 34.6 ± 5.4 and CHD 36.5 ± 5.0 breaths.min−1; p = .106); at the 1st ventilatory threshold (BF@VT-1: AF 23.2 ± 4.6; CHD 22.4 ± 4.6 breaths.min−1; p = .240). %V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\dot{\ ext{V}}}$$\\end{document}O2peak at VT-1 were similar in AF and CHD (AF: 59%; CHD: 57%; p = .656).ConclusionWith the use of wearable technologies on the rise, that now include BF, this first study provides an encouraging potential for BF to be used in AF and CHD. As the supporting data are based on incremental ramp protocol results, further research is required to assess BF validity to manage exercise intensity during longer bouts of exercise.

Effect of Volitional Modification of Breath Frequency on Attention and Mood States: An Exploratory Randomized Crossover Study.

Previously, yoga breathing improved mood states and attention but the effect of varying breath frequency on mood and attention was not clear. The objective of this study was to determine the effects of changes in breath frequency on attention, mood, vigor, and affect states. Thirty participants (mean age ± standard deviation, 27.3 ± 4.2 years) were assessed on 2 separate days practicing either high-frequency yoga breathing (HFYB, breath frequency 54.23/min) or bumblebee yoga breathing (BBYB, breath frequency 3.97/min) in random order. Assessments included blood pressure (BP), cancellation test scores, Nijmegen (to check for hyperventilation), respiration (rate, height of the breath wave [depth], and duration of inhalation relative to exhalation), mood states, vigor, and affect states. Diastolic BP increased after HFYB, whereas systolic BP decreased after BBYB, after both sessions scores in a cancellation test increased (changes in cancellation test performance suggest alertness and test-directed attention), also global vigor (signifying mental energy) and global affect (related to being "happy" and "calm") scores increased, whereas negative mood decreased after HFYB session (P < 0.05, Wilcoxon signed-rank test). Both HFYB and BBYB increased attention test scores, possibly due to cortical activation (HFYB) or relaxation (BBYB). In HFYB, breath frequency and inspiration duration increased suggestive of increased sympathetic activity, accounting for increased vigor, positive affect, and diastolic BP. In contrast in BBYB, low breath frequency, higher breath amplitude, and prolonged expiration suggestive of parasympathetic activity may account for the decreased systolic BP after BBYB.

Conditional activity of parabrachial Tac1 neurons turns on rapid breathing

Breathing is regulated automatically to preserve homeostasis. This reflex regulation of breathing is achieved through neural circuits that function as negative feedback loops. Similar to how a thermostat regulates temperature in a room, the activity of these circuits can be adjusted up or down to fine tune breathing and restore a homeostatic set-point. Yet, breathing is also conditionally altered by behaviors and emotions, requiring dissociation of breathing frequency and pattern from its underlying automatic control. Relatively little is known about the circuits that mediate this “state-dependent'' control. We previously found that optogenetic activation of a Tac1, but not Calca, expressing subpopulation of lateral parabrachial (PBN) neurons drives breathing frequencies that far exceed those relevant for the homeostatic control of breathing. Here, we combine cell-type-specific silencing and multi-unit recording approaches to further test the hypothesis that this circuit plays an important role in state-dependent, but not automatic, respiratory control. To render Tac1 PBN neurons non-functional, the PBN of adult Tac1Cre mice was injected bilaterally with an AAV that drives Cre-dependent expression of tetanus light chain. After allowing ~4 weeks for viral expression, plethysmography did not reveal any differences in breathing frequency or pattern compared to mice injected with control AAV. Changes in breathing were also absent during acute optogenetic inhibition of Tac1+; Calca- neurons following injection of AAV that expresses iC++ in neurons that contain Cre but not FlpO in the PBN of Tac1Cre; CalcaFlpO mice. To assess the spiking activity of Tac1 PBN neurons relative to ongoing breathing patterns, the PBN of Tac1Cre; CalcaFlpO mice was injected with an AAV that expresses ChRmine in neurons containing Cre but not FlpO, a cranial window was created dorsal to the PBN and a head bar secured to the skull. After 2 weeks, mice were head-fixed and a high-density neuropixels probe was inserted into the PBN via the cranial window. Multi-unit activity was recorded from awake, freely breathing mice during simultaneous recording of respiratory pattern. Illumination of the cranial window with red light was suffcient for ChRmine mediated deep brain activation of Tac1+;Calca- PBN neurons, producing a robust increase in breathing frequency. Recorded PBN units were then optically tagged by assessing their response latency and fidelity to repeated 10 ms light pulses. Based on our preliminary observations, “optotagged” Tac1+; Calca- neurons were mostly quiescent during resting breathing but switched to tonic spiking during bouts of sniffng/rapid breathing. Thus, we predict that Tac1 PBN neurons do not regulate breathing via thermostat-like changes in activity similar to breathing reflexes. Instead, Tac1 PBN neurons represent a switch-like mechanism where these neurons are primarily inactive with minimal respiratory role under normal conditions, but when activated they turn on rapid breathing. R01HL166317. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Chronic, episodic nicotine exposure enhances the hypoxic ventilatory response in adult female rats

It is well known that cigarette smoking causes lung disease and damages the airways. However, we know little about the direct role of nicotine, the primary addictive component of tobacco, in the development of smoking- related diseases. Along with promoting cancer cell proliferation and airway inflammation, nicotine can modulate central respiratory control, increasing the rate and depth of breathing through mechanisms that are not well understood. In addition, cigarette smoking is associated with obstructive sleep apnea, a sleep-related breathing disorder that is marked by reduced brainstem respiratory motor output. Despite these examples indicating that chronic nicotine exposure in adulthood may alter central respiratory control, there is no published research that directly tests this hypothesis. We exposed male and female adult rats to nicotine for four weeks through their drinking water and then used whole body plethysmography to test the hypothesis that chronic, episodic nicotine exposure alters restful breathing and the hypoxic ventilatory response (HVR), a critical respiratory chemoreflex. We measured tidal volume (TV) and frequency of breathing at rest, and during a 5- minute episode of hypoxia (10% oxygen/balance nitrogen). Total ventilation (VE/VCO2) was calculated as TV X Frequency and normalized to carbon dioxide production, to account for changes in metabolism, and body weight. For both males and females, comparisons were made between groups and across trials using a 2-way ANOVA and Tukey’s post-hoc test. In male rats, nicotine exposure significantly decreased overall ventilation at rest in one of three trials (Trial 1 VE/VCO2: Nicotine exposed, 30.7±7.5 mL/min/100g, Control, 44.3±6.4 mL/min/100g, p=0.0183), but had no effect on breathing during hypoxia. In female rats, nicotine exposure had no effect on breathing at rest, however, overall ventilation during hypoxia was enhanced in nicotine exposed rats compared to controls in two of three trials (Trial 1 VE/VCO2: Nicotine exposed, 106.8±20.6 mL/min/100g, Control, 79.8±5.1 mL/min/100g, p=0.049; Trial 3 VE/VCO2: Nicotine exposed, 101.6±9.9 mL/min/100g, Control, 68.1±10.9 mL/min/100g, p=0.007). Overall, these results suggest that chronic nicotine exposure triggers plasticity in the chemoreflex pathway mediating the HVR in a sex specific manner and further studies are warranted to understand the implications of this finding. 1K99HL164973-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Characteristics of Cardiorespiratory Failure Preceding Seizure-Induced Mortality in SSKcnj16−/− Rats

Epilepsy is a common, chronic neurological condition characterized by repeated, uncontrolled seizures. These patients are at high risk for cardiorespiratory failure (CRF) and Sudden Unexpected Death in Epilepsy (SUDEP) — the mechanisms of which remain unknown. Most SUDEP events are unwitnessed at night suggesting a circadian influence on seizure-induced mortality. Here we studied cardiorespiratory (CR) function continuously (24/7) in a rat model of audiogenic seizures (SSKcnj16−/− rats) in which repeated seizures have been shown to cause progressive respiratory suppression and mortality. We hypothesized repeated seizures in SSKcnj16−/− rats also lead to 1) progressive dysfunction of post-ictal heart rate (HR) and blood pressure (BP) responses, and 2) cause death via cardiorespiratory failure most frequently when seizures occur after the onset of the inactive period (8am) or prior to the onset of the active phase (4pm). Age matched male and female SSKcnj16−/− rats were implanted with a carotid pressure telemeter and housed in a chronic monitoring plethysmograph with HD video to continuously measure breathing, BP, and HR. Audiogenic seizures (1/day (d) for up to 10d) were induced at a specific time of day and the physiologic data analyzed. Consistent with previous findings, repeated generalized tonic-clonic seizures (GTCSs) caused acute ictal/post-ictal apnea and transient respiratory rate suppression for ~5 minutes post-ictal which was exacerbated with additional seizures (n=6). In addition, GTCSs induced progressively greater transient post-ictal HR suppression and increased BP (n=3; p&lt;0.05 on days 8-10 compared to days 1-3). When seizures occurred at either 8am or 4pm, female SSKcnj16−/− rats had a 10% survival probability (18/20 died) and males had a 40% survival probability (12/20 died). These data combined with previous studies in which seizures were induced throughout the light period showed a higher percentage of deaths at specific times of day: &lt;10am (14%; n=81), 10am-2pm (3%; n=225), 2pm-7pm (8%; n=338). On average seizure-related mortality occurred 2-3 hours after seizures (20 of 30 events) and occurred throughout the 10-day protocol resulting from either moderate (score 2; 53%) or severe (score 3-4; 47%) seizures (Modified Racine Scale). Specific characteristics of death events (n=11-19) included transiently increased BP (+20mmHg) and tidal volume (+0.5 mL/100g; VT) but decreased HR (-50 beats/min), breathing frequency (-50 breaths/min; FB) and ventilation (-20 mL/min/100g; VE). These CR measures then returned to baseline until ~60 minutes post-seizure when there was a secondary decline in BP (-80 mmHg), elevated HR (+100 beats/min), and a concomitant progressive decline in VT and VE prior to terminal apnea/asystole. These data show acute progressive CR suppression with repeated seizures and seizure-induced CRF (tidal volume-mediated decreased ventilation and severe hypotension) leading to death, where time of day for seizure induction contributed to higher mortality rates. This model provides useful insight into the effects of seizures on CR function and understanding the mechanisms of SUDEP, with the ultimate goal of reducing the risk of SUDEP in patients with epilepsy. Supported by NIH HL122358 (MRH). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of high, sub-lethal doses of fentanyl on respiratory functions in adult female goats

Since 1999, the opioid epidemic in the United States has claimed more than 300,000 lives, and data from more recent years indicate annual increases exceeding 80,000 fatalities. Synthetic opioids like fentanyl contribute to these opioid-related deaths through multiple physiologic effects including Opioid-induced respiratory depression (OIRD), impairment of the alveolar to arterial oxygen gradient (A-a), and rigidity of upper airway and pump muscles causing airway dysfunction, or Wooden Chest Syndrome (WCS). We have previously shown (PMID: 37885800) that sub-lethal doses of fentanyl (25-125 μg/kg; IV) cause in healthy adult goats a transient time and dose dependent effect on breathing frequency and tidal volume, WCS and A-a which varied greatly between goats. We hypothesize that high dose fentanyl will exacerbate the effects seen in sub-lethal doses in both a time and dose-dependent manner. Adult female goats (n=3) were surgically instrumented with electromyographic (EMG) wires in both the airway (genioglossus and thyropharyngeal) and respiratory pump muscles (diaphragm, transverse abdominus and diaphragm) and the carotid arteries were relocated to a subcutaneous location. Goats were allowed 2 weeks for recovery before the onset of studies. Arterial blood samples were obtained through carotid catheters and fentanyl injections were made through acute placement of jugular venous catheters. Following a 30-minute control period, we injected saline (vehicle) or high-dose fentanyl (250-500μg/kg). In a time dependent manner, high doses of IV fentanyl injections decreased breathing frequency (FB), increased expiratory time (TE) and increased tidal volume (VT). Arterial oxygen (PaO2) decreased substantially (~35 mmHg; and arterial CO2 (PaCO2) increased to as high as 70mmHg. From about 15 to 90 minutes after fentanyl injections, the overall effect on breathing and respiratory muscle activity was consistent with a stimulatory effect of fentanyl. These data suggest high dose fentanyl increases OIRD and exacerbate life-threatening effects that cause ventilatory suppression, hypoxemia, and hypercapnia. Funded by NIH DA050571. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Understanding the Role of Central Parasympathetic Activation in Opioid-Induced Respiratory Depression and Peripheral Airway Constriction

Opioid-induced respiratory depression (OIRD) is a primary cause of mortality resulting from opioid overdose. Numerous mechanisms have been identified as contributors to OIRD, such as the suppression of central respiratory rhythmogenesis. Our recent research revealed that opioids' ability to suppress breathing extends beyond the central suppression of rhythmic activity, notably leading to airway constriction, which can culminate in complete obstruction. The autonomic nervous system plays a pivotal role in regulating the tone of airway smooth muscles with the parasympathetic system being mainly responsible for bronchoconstriction, and the sympathetic system facilitating bronchodilation. In this study, we evaluated the hypothesis that exposure to fentanyl results in the disinhibition of parasympathetic motor output, leading to centrally mediated peripheral airway constriction. After administering fentanyl (500μg/kg i.p.), minute ventilation dropped by nearly 50%, primarily due to a decrease in breathing frequency. Transient airflow obstructions during the inspiratory phase were observed following fentanyl administration, as indicated by an increased latency between diaphragm contraction and the start of inspiratory flow. These airflow obstructions were fully reversed by the sympathomimetics salbutamol or epinephrine. To determine whether the transient obstructions were a result of vagal activation, another group of mice underwent vagotomy prior to fentanyl administration. The vagotomy effectively eliminated the occurrence of airflow obstructions following fentanyl administration. Additionally, using neuronal activity-based fos-dependent labeling and in-vitro patch-clamp recordings, we showed that fentanyl administration led to a pronounced activation of parasympathetic motor neurons within brainstem areas, including the dorsal motor nucleus of the vagus and the nucleus ambiguus. Collectively, our findings suggest that fentanyl induces transient obstructions to airflow that may be attributed to heightened central parasympathetic activity, which in turn drives peripheral airway constriction. P01 HL090554 (J.M.R.), R01 HL126523 (J.M.R.), R01 HL144801 (J.M.R.), R01 HL151389 (J.M.R.), F32 HL154558 (N.J.B.), R00HL145004 (N.A.B.) and R01HL166317 (N.A.B.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.